Medical procedure kit having medical adhesive

ABSTRACT

A medical procedure kit incorporates one or more surgical tools necessary to perform at least part of a medical procedure, along with a container having a quantity of a medical adhesive. Medical adhesives are useful as an alternate or an adjunct to surgical sutures and/or staples in wound closure, as well as for covering and protecting surface wounds such as lacerations, abrasions, burns, stomatitis, sores, minor cuts and scrapes, and other wounds. As such, the inclusion of such an adhesive into a composite medical procedure kit can be of great assistance to a medical doctor or surgeon by providing in single kit form, tools necessary to complete many medical procedures, without having to use multiple procedure kits. The adhesive may be independently sterilized and wrapped from the other surgical tools of the resultant kit, and then associated into kit form, or assembled and sterilized together as a unitary kit. When the adhesive is incompatible with sterilizing procedures of the other components of the kit, the adhesive may be pre-sterilized and protected by a sterilization barrier that shields the adhesive from exposure to the sterilization process used to sterilize other tools of the procedure kit. The adhesive is preferably a 1,1 -disubstituted ethylene monomer, such as an alpha-cyanoacrylate.

BACKGROUND OF THE INVENTION

[0001] 1. Field of Invention

[0002] The invention relates to sterile medical procedure kits.

[0003] 2. Description of Related Art

[0004] Pre-sterilized medical procedure kits are known and used forvarious medical operating procedures. Such sterilized procedure kits areprovided with a plurality of components used in connection with aparticular surgical procedure. These kits have been used, for example,as suture or wound closure kits, or other procedural kits, includingtools necessary to complete a desired surgical procedure, such asendoscopic or laparoscopic surgery. Such kits include components thatmust be sterilized before or during packaging and must be maintained ina sterile condition until used.

[0005] Sterilization of medical procedure kits and/or its packaging areaccomplished by various methods. These methods include chemical,physical, and/or irradiation methods. Examples of chemical methodsinclude exposure to ethylene oxide or hydrogen peroxide vapor. Examplesof physical methods include sterilization by heat. Examples ofirradiation methods include gamma irradiation, electron beamirradiation, and microwave irradiation.

[0006] U.S. Pat. No. 4,522,302 to Paikoff discloses one knownpre-sterilized medical procedure kit package within an outer packagewrap. The kit includes two compartments, pre-sterilized by ethyleneoxide and wrapped within an inner package wrap. A first compartmentcontains essential medical procedure components, which are subjected toethylene oxide sterilization. A second compartment contains a vial withan agent incompatible with ethylene oxide sterilization, such as a vialwith a rubber stopper. The vial is separately heat sterilized and thensealed inside an ethylene oxide impermeable container and placed in thesecond compartment prior to exposure of the complete kit to ethyleneoxide sterilization.

[0007] Another known procedure kit can be found in U.S. Pat. No.4,523,679 to Paikoff et al., which also discloses a pre-sterilizedmedical procedure kit with at least two compartments. A largercompartment includes medical components for a particular procedure. Asecond smaller compartment can have a cavity open from two sides andsealable by barrier layers. In use, the medical components are placed inthe larger compartment and the barrier layers are provided on thesmaller compartment while the kit is exposed to ethylene oxidesterilization. Then, the kit is removed to a sterile environment and thebarrier layers are removed and a second component, made of rubber andheat sterilized elsewhere, is sealed in the smaller compartment with newsterile barrier layers. The package is then placed in a sterile outerwrap and sealed. This allows a kit to include a component that isincompatible with ethylene oxide sterilization.

[0008] A known surgical suture kit is commercially available from InletMedical Inc. This kit includes a disposable suture passer, a pilotsuturing guide, and braided sutures. Such a kit is intended for use insecuring trocar wounds made during laparoscopic surgery.

[0009] Other suture procedure kits can be found in U.S. Pat.No.5,350,060 to Alpern; U.S. Pat. No. 5,615,766 to Gemma, Jr. et al.;U.S. Pat. No. 5,335,775 to Scanlon et al.; and U.S. Pat. No. 5,282,533to Holzwarth et al.

[0010] Pre-packaged procedure kits including instrumentation forendoscopic surgery can be found in U.S. Pat. Nos. 5,315,985 and5,144,942, both to Decarie et al.; and U.S. Pat. No. 5,375,717 toRoshdy. The Decarie et al. patents provide a procedure kit useful inperforming laparoscopic or endoscopic surgery, including a trocarassembly, an obturator, a sleeve member, a cutting device, a staplingdevice, a dissector, a gripping device, a catheter, and the like.

[0011] U.S. Pat. No. 5,874,044 to Kotzev discloses sterilization ofcyanoacrylate having a package containing the sterile cyanoacrylate. Thepackage is taught to be heat-resistant up to the sterilizationtemperature, while providing an adequate barrier to moisture and beingcyanoacrylate-compatible. The sterilization is achieved using heatsterilization or radiation. Kotzev appears to recognize and teach thatcyanoacrylate formulations have reduced shelf life after being exposedto most types of sterilization.

[0012] U.S. Pat. No. 5,881,536 to Muller-Wille et al. discloses a methodand device for sterile packaging of a substance in a container, wherebythe substance is unable to stand the same sterilization process as theone to which the container is subjected. The method includes sterilizingthe container (not containing the substance) while the container isenclosed in an outer package so that the container becomes internallyand externally sterile; sterilizing the substance with a differentsterilizing process; and inserting the substance into the containerwithout contaminating the container or the substance.

[0013] Monomer and polymer adhesives are used in both industrial(including household) and medical applications. Included among theseadhesives are the 1,1 -disubstituted ethylene monomers and polymers,such as the α-cyanoacrylates. Since the discovery of the adhesiveproperties of such monomers and polymers, they have found wide use dueto the speed with which they cure, the strength of the resulting bondformed, and their relative ease of use. These characteristics have madethe α-cyanoacrylate adhesives the primary choice for numerousapplications such as bonding plastics, rubbers, glass, metals, wood,and, more recently, biological tissues.

[0014] It is known that monomeric forms of α-cyanoacrylates areextremely reactive, polymerizing rapidly in the presence of even minuteamounts of an initiator, including moisture present in the air or onmoist surfaces such as animal (including human) tissue. Monomers ofα-cyanoacrylates are anionically polymerizable or free radicalpolymerizable, or polymerizable by zwitterions or ion pairs to formpolymers. Once polymerization has been initiated, the cure rate can bevery rapid.

[0015] Medical applications of 1,1-disubstituted ethylene adhesivecompositions include use as an alternate or an adjunct to surgicalsutures and/or staples in wound closure, as well as for covering andprotecting surface wounds such as lacerations, abrasions, burns,stomatitis, sores, minor cuts and scrapes, and other wounds. When anadhesive is applied to surfaces to be joined, it is usually applied inits monomeric form, and the resultant polymerization gives rise to thedesired adhesive bond.

[0016] No known commercial sterilized procedure kits (particularlysurgical procedure kits or wound closure kits) include a medicaladhesive, such as a 1,1-disubstituted ethylene monomer (cyanoacrylate).It is believed that this may in part be due to factors involvingsterilization. That is, many medical adhesives degrade to below asatisfactory level after multiple exposures to sterilization processes.However, many known procedure kits require multiple sterilizationprocedures to achieve sterilization of all components within the kit.

SUMMARY OF THE INVENTION

[0017] There is a need for a medical procedure kit that includes amedical adhesive useful in connection with at least a portion of amedical or surgical procedure, such as wound closure. The addition ofsuch an adhesive in a surgical kit would greatly benefit the convenienceof medical procedures, as adhesive wound closure products, such asDermabond® adhesive, available from Closure Medical Corporation ofRaleigh, N.C., can be readily applied to a wound site and are extremelyeffective as part of a wound closure system. Such a procedure kit isparticularly useful when packaged with a procedure kit for laparoscopicor endoscopic surgery. However, heretofore, such a procedure kit has notbeen realized in the commercial market.

[0018] Applicant has overcome the above and other problems by thepresent invention, which provides a medical adhesive as part of asterilized surgical procedure kit.

[0019] According to one aspect of the invention, all components of theprocedure kit but the adhesive and applicator are packaged in kit formand sterilized. Then, the adhesive and optionally an adhesive applicatorare separately sterilized and packaged, with the resultant twosterilized packages being associated so as to provide one convenient,combined medical procedural kit that can be brought into an operatingroom or other sterile environment to be used.

[0020] According to another aspect of the invention, the adhesive andoptionally an adhesive applicator are sterilized and placed in asterilization barrier, such as a foil barrier impervious to a certaintype of sterilization procedure, and the sterilization barriercontaining the adhesive is provided along with remaining components ofthe procedure kit in kit form and subsequently exposed to sterilization,such as exposure to ethylene oxide, to sterilize the entirety of thecontents. In this embodiment, as the adhesive is contained within thesterilization barrier, the adhesive is not subjected to multiplesterilization processes and thus may prevent possible degradation orpolymerization due to over exposure to sterilization processes.

[0021] According to yet another aspect of the invention, the adhesiveand applicator are placed along with all remaining components into theprocedure kit, and are subsequently subjected to one or moresterilization processes. However, in accordance with this aspect, themedical adhesive and applicator are formulated to withstand the appliedsterilization process without degradation to below product specificationparameters. That is, there is substantially no initiation ofpolymerization of monomeric liquid adhesive compositions that wouldsubstantially affect the utility or shelf-life of the monomer ormonomers.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The foregoing and other features and objects of the inventionwill become apparent from the following drawings and description, whichdetail exemplary embodiments of medical procedure kits, in which:

[0023]FIG. 1 shows a top view of an exemplary medical procedure kitaccording to a first embodiment of the invention;

[0024]FIG. 2 shows a side view of the procedure kit of FIG. 1;

[0025]FIG. 3 is an alternative exemplary medical procedure kit, usefulin endoscopic or laparoscopic surgery, according to the invention;

[0026]FIG. 4 is a flow chart detailing a sterilization process accordingto a first embodiment of the invention;

[0027]FIG. 5 shows a top view of an exemplary medical procedure kitaccording to a modified first embodiment of the invention;

[0028]FIG. 6 shows a cross-sectional side view of the procedure kit ofFIG. 5 taken along line 6-6;

[0029]FIG. 7 is a flow chart detailing a sterilization process accordingto the modified first embodiment of the invention;

[0030]FIG. 8 shows a top view of an exemplary medical procedure kitaccording to a second embodiment of the invention;

[0031]FIG. 9 shows a side view of the procedure kit of FIG. 8;

[0032]FIG. 10 shows an alternative side view of the procedure kit ofFIG. 8;

[0033]FIG. 11 is a flow chart detailing a sterilization processaccording to the second embodiment of the invention;

[0034]FIG. 12 shows a top view of an exemplary medical procedure kitaccording to a third embodiment of the invention;

[0035]FIG. 13 shows a side view of the procedure kit of FIG. 12;

[0036]FIG. 14 shows an alternative side view of the procedure kit ofFIG. 12;

[0037]FIG. 15 is a flow chart detailing a sterilization processaccording to the third embodiment of the invention; and

[0038]FIG. 16 shows an exemplary applicator/container for use in storingand applying a medical adhesive according to the invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0039] With reference to FIGS. 1-3, a medical procedure kit 100according to a first aspect of the invention is provided. The kit 100shown in FIG. 1 includes a first portion 100 containing one or moresurgical or medical tools 110 (tools 110A-110D shown) necessary toperform a particular medical or surgical procedure. This can be most anytype of surgical or medical equipment or tools such as, for example,surgical forceps (110A), surgical scissors (110B), and surgical scalpelsof various configurations (110C, 110D). Such tools can also tools suchas those shown in the procedure kit of FIG. 3, including surgicaldevices (110E) useful for operating within trocars (110G), obturators(110F), endoscopic wound closure devices (110I, 110H), and applicatorsand/or parts (110J). Other non-limiting examples of non-illustratedtools include surgical sponges, syringes, anesthetics, needles, clamps,cannulas, vials, gauze pads, swabs, stapling devices, dissectors, andsutures to name a few.

[0040] Referring back to FIGS. 1-2, the tool 110 may be provided on atray 115 and are wrapped or covered by an outer wrap or covering 120.Non-limiting examples of suitable covering materials include Tyvek®(HDPE), paper or PVC film. The covering may be as shown to cover theopen top of the tray 115. However, it is also possible for the covering120 to completely enclose tray 115. In such an embodiment, outer wrap120 may be in the form of an open-ended tube, with ends being sealed,such as by a heat seal or glue seal, after insertion of the tray andtools within the outer wrap 120. Alternatively, it is possible to have aprocedure kit 100 without the tray 115. In such a case, the outer wrapwould fully extend around the tools 110 to seal them (similar to that ofFIG. 10 only without tray 115).

[0041] The kit 100 according to the first embodiment also includes asecond portion 100B provided with one or more containers 140 having amedical adhesive 150. The container 140 may be a single-use crushableampoule or more preferably is an adhesive container/applicator thatincludes an applicator tip and body for dispensing the adhesive onto asurgical site, such as body tissue. Also, optionally separateapplicator(s) and containers with adhesive can be provided. The medicaladhesive 150 and container 140 are sealed within a suitable cover 160,which also is preferably formed from Tyvek® (HDPE), paper or PVC film.

[0042] The medical adhesive 150 used in any of the embodiments of theinvention may include adhesive compositions known in the art orhereafter developed for use in connection with a medical or surgicalprocedure, including, but not limited to, polymerizable monomericadhesives. Preferred monomer compositions of the present invention, andpolymers formed therefrom, are useful as tissue adhesives, sealants forpreventing bleeding or for covering open wounds, and in other biomedicalapplications. They find uses in, for example, apposing surgicallyincised or traumatically lacerated tissues; retarding blood flow fromwounds; dressing burns; dressing skin or other superficial or surfacewounds such as compromised skin or other tissue (such as abrasions,chaffed or raw skin, minor cuts and scrapes, sores and/or stomatitis);protecting intact skin; and aiding repair and regrowth of living tissue.

[0043] Preferred monomers that may be used in this invention are readilypolymerizable, e.g. anionically polymerizable or free radicalpolymerizable, or polymerizable by zwitterions or ion pairs to formpolymers. Such monomers include those that form polymers, that may, butdo not need to, biodegrade. Such monomers and associated adhesivecompositions are disclosed in, for example, U.S. Pat. No. 5,328,687;5,259,835, 5,624,669, 5,328,687, 5,928,611; 2,721,858; 3,254,111;4,364,876; 3,554,990; 5,582,834; 5,575,997; 5,514,371; 5,514,372; and3,940,362, all of which are hereby incorporated by reference herein intheir entirety. They are also disclosed in the following co-pending U.S.patent applications Ser. Nos. 09/374,207, 08/609,921, 081714,288,08/909,845, 08/755,007, 08/920,876, 09/025,472, 09/099,457, and09/471,392, all of which are incorporated by reference herein in theirentirety.

[0044] A particularly suitable adhesive is a 1,1-disubstituted ethyleneadhesive composition. Medical applications of 1,1-disubstituted ethyleneadhesive compositions include use as an alternate and an adjunct tosurgical sutures and staples in wound closure as well as for coveringand protecting surface wounds such as lacerations, abrasions, bums,stomatitis, sores, and other open surface wounds.

[0045] Preferred monomers are alkyl alpha-cyanoacrylates and morepreferably octyl alpha-cyanoacrylates, especially ethyl butyl or 2-octylalpha-cyanoacrylate. Monomers used in the present application shouldpreferably be very pure and contain few impurities (e.g., surgicalgrade).

[0046] Referring back to FIGS. 1-3, each individual kit portion (100A,100B) can be separately assembled and sterilized and then associatedinto a combined procedural kit form by suitable affixing methods, suchas stapling, heat bonding and the like. Another overwrap may optionallybe provided to filly enclose both the kit portions (100A, 100B).

[0047] Sterilization of the medical adhesive and its packaging can beaccomplished by techniques known to the skilled artisan, and ispreferably accomplished by methods including, but not limited to,chemical, physical, and/or irradiation methods. Examples of chemicalmethods include, but are not limited to, exposure to ethylene oxide orhydrogen peroxide vapor. Examples of physical methods include, but arenot limited to, sterilization by heat (dry or moist) or retort canning.Examples of irradiation methods include, but are not limited to, gammairradiation, electron beam irradiation, and microwave irradiation. Apreferred method is electron beam irradiation or exposure to ethyleneoxide. In embodiments where a composition is to be used for medicalapplications, the sterilized composition must show low levels oftoxicity to living tissue during its useful life.

[0048] An exemplary assembly and sterilization process is shown in FIG.4. The process starts at step S400 and advances to step S410 where thetray is provided and one or more pre-sterilized tools 110 are placed inthe tray. Then at step S420 , covering 120 is bonded to tray 115 toprovide a sealed enclosure (first portion 100A) housing the tools 110.Then, at step S430, the first portion 100A is subjected to sterilizationto sterilize the entire portion 100A and its contents. This may be, forexample, by exposure to ethylene oxide or any other suitablesterilization process. In the case of ethylene oxide, the outer covering120 will be of a material, such as plastic, that allows penetration ofthe ethylene oxide so as to be able to sterilize the tray 115 and tools110.

[0049] Then, at step S440, one or more containers 140 having a medicaladhesive 150 therein are provided, which may be non-sterilized orpre-sterilized. From step S440, flow advances to step S450, where outercovering 160 is provided to fully cover the containers and provide thesecond kit portion 100B. Covering 160 may be of a plastic materialhaving ends that are heat sealed, glued or otherwise sealed. After stepS450, flow advances to step S460 where the second kit portion 100B issterilized by a sterilization process, such as exposure to ethyleneoxide or gamma radiation, although the aforementioned othersterilization methods could alternatively be used. After step S460 ,flow advances to step S470 where the two kit portions 100A and 100B areaffixed to form a final medical procedure kit 100. Suitable affixing canbe by numerous methods, such as stapling, heat sealing, gluing, or thelike. The final medical procedure kit 100 provides a single kit thatcontains all essential tools (both tools 110 and adhesive 150) toperform all or at least a particular part of a specified medicalprocedure. The process then stops at step S480. This kit is convenientto use as only one item needs to be brought into the sterile surgicalenvironment and a surgeon or doctor can have ready access to allequipment necessary to perform a desired procedure.

[0050] With this embodiment, the two kit portions 100A, 100B can beassembled and sterilized separately, allowing parallel processing, ifdesired, and use of differing sterilization procedures. This isimportant where the medical adhesive 150 is unable to withstandsterilization procedures necessary for sterilization of the other tools,or where multiple sterilization processes would degrade one or moreproperties of the adhesive.

[0051] An alternative arrangement is provided in FIGS. 5-6. In thisalternative, the tray 115 is omitted and the tools 110 (100A-100D) aresealed within covering 120. When the medical adhesive 150 is not capableof withstanding multiple sterilization exposure or the particularsterilization process used to sterilize the tools, the tools 110 aresealed in a first portion 100A of the kit and a second portion 100B isinitially provided with an open end (far left end). A heat seal or glueseal or other sealing means 130 is provided to separate the kit 100 intothe first and second portions. After sterilization of the tools 110within the first portion 100A, the adhesive 150 within containers 140can be provided to the second portion l00B and the open end heat sealed,such as by sealing means 130. The entire kit 100 may then be sterilizedto sterilize the adhesive, or the containers 140 and adhesive 150 may bepre-sterilized.

[0052] A process of assembling and sterilizing the procedure kit 100according to this modified embodiment is shown in FIG. 7. The processstarts at step S700 and advances to step S710 where one or more tools110 (non-sterilized or pre-sterilized) are provided within outercovering 120. Then at step S720, the covering has an intermediateportion sealed at 130 by a heat seal, glue seal or other sealing methodto divide the outer covering into a first portion 100A containing thetools 110 (which is now sealed), and a second portion 100B that is openon one end. Then, at step S730, the first portion 100A is subjected tosterilization to sterilize the entire portion 100A and its contents.This may be, for example, by exposure to ethylene oxide or any othersuitable sterilization process. In the case of ethylene oxide, the outercovering 120 will be of a material, such as plastic, that allowspenetration of the ethylene oxide so as to be able to sterilize theinterior of covering 120 and tools 100.

[0053] Then, at step S740, one or more containers 140 having a medicaladhesive 150 therein are provided within the second portion 100B. Thesecontainers may be non-sterilized or pre-sterilized. From step S740, flowadvances to step S750, where the open end of the second portion 100B issealed by a heat seal or other heat sealing means 130′ to fully enclosethe containers 140 within the second kit portion 100B. After step S750,flow advances to step S660 where the second kit portion 100B mayoptionally be sterilized by a sterilization process, such as exposure toethylene oxide or gamma radiation, although the aforementioned othersterilization methods could alternatively be used. This step may not benecessary if pre-sterilized containers are inserted into the secondportion 100B while the kit 100 remains in a sterile environment. Afterstep S760, flow advances to step S770 where the process stops. The finalmedical procedure kit 100 again provides a single kit that contains allessential tools (both tools 110 and adhesive 150) to perform all or atleast a particular part of a specified medical procedure.

[0054] With reference to FIGS. 8-11, a medical procedure kit 100according to a second aspect of the invention is provided. The kit 100rather than providing a first portion and a second portion, insteadconsists of a single portion containing one or more surgical or medicaltools 110 (tools 110A-110D shown) necessary to perform a particularmedical or surgical procedure. The tools can be any medical or surgicaltool necessary to perform a part of a medical or surgical procedure. Thetools 110 may be provided on a tray 115 and are wrapped or covered by anouter wrap or covering 120, which is the same as in the firstembodiment. The covering may be as shown to cover the open top of thetray 115 . However, it is also possible for the covering 120 tocompletely enclose tray 115, as shown in FIG. 10. In such an embodiment,outer wrap 120 may be in the form of an open-ended tube, with ends 125being sealed, such as by a heat seal or glue seal, after insertion ofthe tray and tools within the outer wrap 120. Alternatively, it ispossible to have a procedure kit 100 without the tray 115. In such acase, the outer wrap would fully extend around the tools 110 to sealthem (as shown in FIG. 10 only without tray 115).

[0055] The kit 100 according to the second embodiment is also providedwith one or more containers 140 having a medical adhesive 150, such as,for example, an alpha-cyanoacrylate, therein. The container 140 may be asingle-use crushable ampoule or more preferably is an adhesivecontainer/applicator that includes an applicator tip and body fordispensing the adhesive onto a surgical site, such as body tissue. Inthis embodiment, the adhesive 150 or components thereof may beincompatible with sterilization processes necessary to completesterilization of the remainder of the kit. To accommodate this, theadhesive 150 is pre-sterilized by a suitable sterilization process thatdoes not adversely affect the adhesive and then is packed within orsurrounded by a sterilization barrier 170, which seals or provides aprotective barrier for the adhesive that protects it from penetration ofa particular type of sterilization subsequently used to sterilize theremainder of the kit's contents (i.e., the interior of covering 120 andtools 110). In the case of sterilization by exposure to ethylene oxide,a suitable barrier may be a container or wrap formed from a metal foil,such as aluminum, or a glass or metal container impermeable by ethyleneoxide. A metal foil or metal container would also protect against mostother sterilization processes as well. The container 140 itself may formprotective barrier 170.

[0056] In this embodiment, the entire kit 100 can be assembly andsterilized at one time, even if the particular medical adhesive 150 orcomponents thereof are adversely affected by the particularsterilization used as the sterilization barrier 170 protects theadhesive.

[0057] A process of assembling and sterilizing the kit according to thesecond embodiment will be described with reference to FIG. 11. Theprocess starts at step S1100 and advances to step S1110 where one ormore tools 110 are provided within tray 115. Then at step S1120, one ormore pre-sterilized containers 140 having a medical adhesive 150 thereinare provided with a protective sterilization barrier 170 and placed intothe tray 115. Then, at step S1130, covering 120 is formed over tray 115to seal the tray and provide a sealed enclosure containing the tools andadhesive. From step S1130, flow advances to step S1140 where the entirekit 100 is subjected to sterilization to sterilize the entire kit andits contents. This may be, for example, by exposure to ethylene oxide orany other suitable sterilization process. In the case of ethylene oxide,the outer covering 120 will be of a material that allows penetration ofthe ethylene oxide so as to be able to sterilize the interior ofcovering 120 and tools 110. However, because of the provision of thesterilization barrier 170, the adhesive is protected from furtherexposure to the sterilization process. As such, even though the adhesive150 may be incompatible and adversely affected by the particularsterilization process necessary or desired to sterilize tools 110,adhesive 150 can nonetheless be provided within the same procedure kit.After step S1140, flow advances to step S1150 where the process stops.

[0058] A third embodiment of the invention will be described withreference to FIGS. 12-15. The kit 100 as in the second embodimentconsists of a single portion containing one or more surgical or medicaltools 110 (tools 100A-110D shown) necessary to perform a particularmedical or surgical procedure. The tool 110 may be provided on a tray115 and are wrapped or covered by an outer wrap or covering 120, whichas in previous embodiments is preferably plastic. The covering maybe asshown to cover the open top of the tray 115. However, it is alsopossible for the covering 120 to completely enclose tray 115, as shownin FIG. 14. In such an embodiment, outer wrap 120 may be in the form ofan open-ended tube, with ends 125 being sealed, such as by a heat sealor glue seal, after insertion of the tray and tools within the outerwrap 120. Alternatively, it is possible to have a procedure kit 100without the tray 115. In such a case, the outer wrap would fully extendaround the tools 110 to seal them (as shown in FIG. 14 only without tray115).

[0059] The kit 100 according to the third embodiment is also providedwith one or more containers 140 having a medical adhesive 150, such as,for example, an alpha-cyanoacrylate, therein. The container 140 may be asingle-use crushable ampoule or an adhesive container/applicator thatincludes an applicator tip and body for dispensing the adhesive onto asurgical site, such as body tissue. In this embodiment, the adhesive 150or components thereof are selected to be compatible with sterilizationprocesses necessary to complete sterilization of the remainder of thekit. That is, the adhesive will not degrade below an acceptable amountdue to the sterilization process. In this embodiment, the entire kit 100can be assembly and sterilized at one time.

[0060] A process of assembling and sterilizing the kit according to thethird embodiment will be described with reference to FIG. 15. Theprocess starts at step S1500 and advances to step S1510 where one ormore tools 110 are provided within tray 115. Then at step S1520, one ormore containers 140 having a medical adhesive 150 therein are placedinto the tray 115. Then, at step S1530, covering 120 is formed over tray115 to seal the tray and provide a sealed enclosure containing the toolsand adhesive. From step S1530, flow advances to step S1540 where theentire kit 100 is subjected to sterilization to sterilize the entire kitand its contents. This may be, for example, by exposure to ethyleneoxide or any other suitable sterilization process. In the case ofethylene oxide, the outer covering 120 will be of a material, such asplastic, that allows penetration of the ethylene oxide so as to be ableto sterilize the interior of covering 120 and tools 110. As the adhesiveis selected to have a formulation that withstands exposure to thesterilization process, the entire procedure kit can be sterilized in asingle operation. After step S1540, flow advances to step S1550 wherethe process stops.

[0061] The invention is particularly suited towards use as an endoscopicor laparoscopic surgery and recovery procedure kit, a non-limitingexample of which is shown in FIG. 3. Kit 100 of FIG. 3 may include, forexample, a trocar device 110G, an obturator 110F, a surgical instrument110E operable through the trocar device to perform laparoscopic orendoscopic surgery, a vial 140 containing a quantity of medical adhesive150, and a wound closure device (110H, 110 I, 110J) used to close aninternal wound or tissue site within a body after surgery is complete.An exemplary wound closure device can be found in co-pending U.S. patentapplication No. 09/450,686 filed Nov. 30, 1999 entitled “Applicator forLaparoscopic or Endoscopic Surgery”, the subject matter of which isincorporated herein by reference in its entirety. Such a wound closuredevice includes a pump member 110H, an extension member 110I extendiblethrough an endoscopic pathway or trocar, and one or more replaceabletips 110J. The tips 110J are placed on the end of extension member 110Iand can be filled with a quantity of adhesive 150 from vial 140 (orprefilled with adhesive, in which case vial 140 maybe unneeded). Byproviding a wound closure device and medical adhesive within anendoscopic medical procedure kit, the entire surgical procedure,including wound closure upon completion can be performed using the toolsprovided within a single procedure kit. This greatly simplifies theoperating room procedure.

[0062] The medical adhesive 150 is preferably provided in a container140 that serves as an applicator/dispenser. An exemplary applicatordispenser 140 will be described with reference to FIG. 16. Preferredembodiments provide a monomer adhesive 150 within a crushable glassampoule 142, which can serve as container 140. However, it is preferablefor the container to provide an applicator function as well. To achievethis, glass ampoule 142 with an adhesive 150 therein may be containedwithin a flexible applicator body 144, through which the crushableampoule can be crushed by finger pressure. The applicator body 144includes a tip 146 that allows dispensing of the adhesive from withinapplicator body 144 upon crushing of the ampoule. In preferredembodiments of the invention, when the composition is analpha-cyanoacrylate, the tip 146 may have on or in it a polymerizationinitiator or rate modifier, e.g., accelerator or inhibitor, whichassists the cyanoacrylate adhesive to polymerize quickly and completelyas well as allowing the operator to apply the adhesive in severalsuccessive layers which will be advantageous for applications requiringhigh tensile strength. The tip may additionally or alternatively containa bioactive material. Examples of applicators, applicator tips anddispensers useable in the present invention can be found in U.S. Pat.No. 5,928,611 and co-pending U.S. patent applications Nos. 09/069,979filed Apr. 30, 1998, 09/176,889 filed Oct. 22, 1998, 09/447,045 filedNov. 23, 1999, 09/219,851 filed Dec. 23, 1998, 09/430,290 filed Oct. 29,1999, and 09/385,030 filed Aug. 30, 1999, the disclosures of which areincorporated herein by reference in their entirety.

[0063] Various exemplary monomer adhesive formulations were tested forstability and compatibility with single or multiple exposures to varioussterilization procedures in order to determine the feasibility ofplacing medical adhesives into a sterilized procedure kit. The testsused three different sterilization processes: process cycle Q; processcycle R; and process cycle S, which are described below in detail.

[0064] Cycle Q uses OXYFUME 2000 (8.6% EO and 91.4% HCFC) as thesterilant. Preconditioning of product prior to sterilization occurs at arelatively high percent relative humidity (70-95%RH) for twelve hours upto six days. Product is then moved into a sterilization chamber, wherethe validated temperature range of the cycle is not greater than 57° C..Exposure gas dwell time is validated for 3 to 8 hours. Aftersterilization, the gas is removed from the chamber by allowing the gasto exit through an exhaust system. A vacuum is pulled on the product andthen filtered air is injected into the chamber and released toatmospheric pressure. This series of “air rinses” is conducted once.

[0065] Cycle R uses 100% ethylene oxide (EO) gas as the sterilant withwashes of Nitrogen to remove any oxygen from the sterilization chamber.Pre-conditioning is from 6 to 24 hours at a much lower humidity rangethan cycle Q (40-57%RH). Sterilization cycle temperature is slightlylower than cycle Q at 43-52° C.. Oxygen elimination from the chamber isperformed by pulsing nitrogen gas into the chamber a minimum six timesand holding for a dwell period of 4 to 6 minutes. After the last pulseof nitrogen gas, an automatic oxygen analyzation instrument checks theoxygen level in the chamber. The oxygen level must pass before the cyclewill progress into EO injection. If the oxygen test passes, morenitrogen is added to the chamber at a predetermined pressure, and thenEO gas is injected. Gas dwell time is validated for 2 to 3 hours. EO gasis removed from the chamber by exhausting the gas in the chamber throughthe vent, pulling a deep vacuum, and the injecting nitrogen into thechamber. This nitrogen injection is held for 145 to 155 minutes and thenallowed to evacuate through the exhaust system. This is performed atotal of twelve times. After the nitrogen flushes, the chamber isreleased to atmospheric pressure.

[0066] Cycle S uses a sterilant comprising 10% EO and 90.0% HCFC.Preconditioning of product prior to sterilization occurs at a relativehumidity (40-80%RH) for at least 24 hours, preferably 24-48 hours, at atemperature of between 30-50° C.. Product is then moved into asterilization chamber, where the validated temperature range of thecycle is not greater than 52° C.. Exposure gas dwell time is validatedfor 6 hours and 15 minutes to 6 hours and 45 minutes at a relativehumidity of between 45-75% and a pressure between 9.5-11.5 psig. Aftersterilization, the gas is removed from the chamber by allowing the gasto exit through an exhaust system. A vacuum is pulled on the product(20-24″Hg) six times and then filtered air is injected into the chamberand released to atmospheric pressure. This series of “air rinses” isconducted once at a temperature of between 21-43° C. for 12-48 hours.

[0067] Table 1 provides setting times and temperatures for samples of astandard production of (non-sterile) Dermabond® adhesive exposed to afirst sterilization cycle (1X), a second sterilization cycle (2X) and athird sterilization cycle (3X) using a same ethylene oxide cycle (Rcycle). This test was conducted to establish whether set times and settemperatures would substantially change so as to exceed acceptablestandards. The set time of the medical adhesive should be no more than 5minutes, preferably less than 2.5 minutes, and more preferably less than2 minutes, or even as low as 1.5 minutes or 1 minute. The medicaladhesive will increase its temperature upon setting and preferablyshould have a set temperature of less than 90° C., more preferably lessthan 75° C.. As the adhesive is preferably topically applied to humantissue during a medical procedure, the set temperature should be chosento be low enough to prevent a burning or irritation to the tissue. As aresult of this testing, it was determined that all lots met acceptablestandards, even after exposure to multiple sterilization cycles (up to3X). TABLE 1 Setting Time and Setting Temperature for Adhesive Exposedto Sterilization Using The Same Ethylene Oxide Cycle 1X 2X 3X Time TempTime Temp Time Temp LOT # (sec) (° C.) (sec) (° C.) (sec) (° C.) A 90 35 92 40 133 32 B 92 35 115 32 141 27 C 87 37 114 34 145 25 AVE. 90 36 10735 140 28

[0068] Table 2 shows the levels of residuals remaining after exposure to1X, 2X or 3X cycles of ethylene oxide sterilization. Detected residualson exposed materials after sterilization included ethylene oxide (EO),ethylene chlorohydrin (ECH) and ethylene glycol (EGly). EGly possiblyoccurs due to hydrolysis of ethylene oxide (C₂H₄O+H₂O→OH—CH₂—CH₂—OH).ECH possibly occurs due to the reaction of ethylene oxide with chlorineions (C₂H₂O+Cl→OH—CH₂-CH₂—Cl) and/or EGly with HCFC(OH—CH₂—CH₂—OH+HCFC→OH—CH₂—CH₂—Cl). Acceptable residual amount limitsare EO <250 ppm, ECH <250 ppm, and EGly <5000 ppm. As a result of thetesting, all lots were found to have acceptable levels of residuals.TABLE 2 Level of Residuals (EO, ECH and EGly) After Ethylene OxideExposures 1X 1X 1X 2X 2X 2X 3X 3X 3X LOT # EO ECH EGly EO ECH EGly EOECH EGly A <3 10 16 <3 6 29 <3 5 44 B <3 13 16 <3 8 32 <3 3 41 C <3  516 <3 5 29 <3 5 41 AVE. <3 10 16 <3 6 30 <3 4 42

[0069] Table 3 shows set times and set temperatures for adhesiveformulations after first (1X), second (2X) and third (3X) cycles ofsterilization, again using the same sterilization cycle, in which theconcentration of monomer initiators present in the adhesive formulationwas varied. In particular, the initiator concentration was increased in25 ppm increments from samples E to I, up to 280 ppm. The initiator usedwas a quaternary ammonium salt/acetone mixture. As a result of thistesting, it was found that all lots met acceptable standards for settime and set temperature. TABLE 3 Set Time and Temperature Results forAdhesive With Variable Initiator Concentrations With Exposure toMultiple Ethylene Oxide Cycles 1x 1x 2X 2X 3X 3X Time Temp Time TempTime Temp SAMPLE (sec) (° C.) (sec) (° C.) (sec) (° C.) E 133 27 103 25147 25 F 131 31 144 27 107 27 G 111 30 150 27 150 24 H 101 32 134 32 14627 I 110 41 127 28 150 25

[0070] Table 4 shows results of another series of adhesive compositions(lots J, K and L) that were exposed to up to three sterilizationprocesses. This experimental data was generated by exposing a standardproduction Dermabond® ) adhesive product to a single ethylene oxidecycle (cycle S). The product from this cycle was then divided and eachset was put through a second cycle of either cycle Q or cycle R. Thisproduct was then put through a third cycle, which was an identical cycleto the one the product previously went through in the second cycle. Theproduct was sampled after each cycle. This shows that the product cannot only be exposed to multiple sterilization cycles, but can be exposedto multiple different cycles and still set in an appropriate timeframeand set temperature. TABLE 4 Setting Time and Setting Temperature forAdhesive Exposed to Sterilization Using Varied Ethylene Oxide Cycles 1x2X 2X 3X 3X Cycle S Cycle M Cycle J Cycle M Cycle J Time Temp Time TempTime Temp Time Temp Time Temp Lot # (sec) (° C.) (sec) (° C.) (sec) (°C.) (sec) (° C.) (sec) (° C.) J 46 69 52 64 44 64 65 53 45 60 K 52 51 5660 48 57 69 45 48 55 L 59 51 68 53 55 50 77 38 58 50

[0071] While the invention has been described with reference topreferred embodiments, the invention is not limited to the specificexamples given, and other embodiments and modifications can be made bythose skilled in the art without departing from the spirit and scope ofthe invention.

What is claimed is:
 1. A method of packaging and sterilizing a medicalprocedure kit containing at least one surgical tool necessary to performa desired medical procedure and a container having a medical adhesive,the method comprising: placing said at least one surgical tool within anouter wrap; placing said container with said adhesive within an outerwrap; sterilizing said at least one surgical tool without significantlydegrading properties of said adhesive; and forming a combined medicalprocedure kit in which said at least one surgical tool and saidcontainer with said adhesive are associated.
 2. The method of claim 1,wherein said at least one surgical tool and said container with saidadhesive are placed within different outer wraps.
 3. The method of claim2, wherein said at least one surgical tool and said container with saidadhesive are associated by affixing said two different outer wraps toeach other.
 4. The method of claim 2, wherein said at least one surgicaltool and said container with said adhesive are sterilized separately. 5.The method of claim 4, wherein the container with said adhesive issubjected to a different sterilization process than said at least onesurgical tool.
 6. The method of claim 1, wherein said at least onesurgical tool and said container with said adhesive are placed within asame said outer wrap.
 7. The method of claim 6, wherein the containerwith said adhesive is subjected to a same sterilization process as saidat least one surgical tool.
 8. The method of claim 7, wherein saidsterilization is by either exposure to ethylene oxide, gamma radiationor electron beam radiation.
 9. The method of claim 6, further comprisingpre-sterilizing said container with said adhesive and providing asterilization barrier around said adhesive prior to sterilizing of saidat least one surgical tool.
 10. The method of claim 9, wherein saidadhesive is sterilized by an electron beam and the entire procedure kitis subjected to ethylene oxide sterilization to sterilize said at leastone surgical tool, the sterilization barrier shielding said adhesivefrom said ethylene oxide sterilization.
 11. The method of claim 9,wherein said container defines said sterilization barrier.
 12. Themethod of claim 6, wherein the at least one surgical tool is sterilizedby subjecting the entire procedure kit to sterilization.
 13. The methodof claim 12, wherein said adhesive is protected from this sterilizationby a sterilization barrier.
 14. The method of claim 12, wherein thesterilization is by exposure to ethylene oxide, gamma radiation orelectron beam radiation.
 15. The method of claim 1, wherein at least theat least one surgical tool is subjected to multiple sterilizationcycles.
 16. The method of claim 1, wherein said adhesive is apolymerizable monomeric adhesive.
 17. The method of claim 16, whereinthe monomer is a 1,1-disubstituted ethylene monomer.
 18. The method ofclaim 16, wherein the monomer is an alpha-cyanoacrylate.
 19. The methodof claim 1, further comprising providing the container with an adhesiveapplicator.
 20. The method of claim 19 further comprising providing theadhesive applicator with an initiator tip.
 21. The method of claim 1,further-comprising a step of sterilizing the adhesive.
 22. The method ofusing the combined medical procedure kit formed in claim 1, comprising:opening the package to expose said at least one surgical tool and saidcontainer with said adhesive; and using said surgical tool and applyingsaid adhesive as part of a medical procedure.